The rapidly dividing intestinal epithelium is very sensitive to damage due to ischemia, chemotherapy or irradiation. The resulting epithelial injury leads to important metabolic and structural alterations in a variety of intestinal cells that can eventually cause cell destruction and death. Despite the fact that restitution of blood flow is necessary to limit the progression of cellular injury associated with ischemia, restoration of blood flow and oxygenation to the ischemic intestine can result in a paradoxical enhancement of tissue injury (reperfusion injury). Chemotherapeutic agents exert their cytoablative actions on rapidly proliferating cells via several different mechanisms, ultimately leading to cell cycle arrest and/or cellular apoptosis. The cytotoxic actions of chemolytics/chemotherapeutic agents are not tumor-specific. Gastrointestinal toxicity following the administration of chemolytics is characterized by severe mucositis, weight loss and systemic infection. Limitation in dose and treatment of chemolytic agents due to gastrointestinal (GI) toxicity impair the effectiveness of chemotherapy in susceptible patients.
The use of multimodality therapies that include radiation have become commonplace in treating many malignancies—about one half of patients with cancer receive radiation therapy as a component of their treatment. Modern techniques for tomographic localization and fractionation of radiation therapy have significantly reduced short-term and long-term gastrointestinal morbidity resulting from radiation therapy. Nevertheless, most patients experience GI symptoms associated with acute radiation therapy, such as diarrhea, abdominal pain, bloating, tenesmus, and bleeding. Chest pain, dysphagia, and odynopagia may be seen when the radiation fields involve the upper GI tract. Usually these symptoms resolve shortly after radiation treatment ends. However, up to one fourth of patients who receive radiation therapy also develop some form of chronic injury, defined as symptoms presenting more than three months after completion of therapy. Symptoms are usually evident within the first two years after initiation of therapy. However, some patients do not develop symptoms for years or even decades.
Exposure of the skin to ultraviolet (UV) light cans produce immediate as well as long-term effects. The predominant acute effects of exposure to UV light include sunburn and vitamin D synthesis. Chronic exposure to UV light can produce photodamaged skin which exhibits wrinkling blotchiness, telangiectasia and a roughened, weather-beaten appearance as well as the more serious consequence of the development of melanoma or nonmelanoma skin cancer. Although the risk of skin cancer does not correlate well with cumulative exposure to UV light, skin cancers are generally considered long-term sequela of exposure to UV light.
A cutaneous wound may take 12 to 18 months to fully repair and scarring is the result of an injury that causes an exaggerated healing response that interferes with proper wound healing. Scars may be result of wounds, burns, surgeries, accidents and may be caused by bacteria and skin conditions such as acne.
There is need for therapies that provide a treatment regimen that is effective in inhibiting epithelial injury related cell death and promoting cell survival.